Emeritus Faculty - University Medical Line, Pediatrics
Current Research and Scholarly Interests
Neonatology, neurobehavioral development, outcomes in premature infants.
Length of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants: effects on neonatal adaptation and psychomotor development
2011; 217 (2): 211-219
This study evaluated the question whether length of in utero exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants might affect neonatal outcome and psychomotor development in infancy.Birth outcome was determined in the offspring of 55 women with major depressive disorder who used SSRI medication for different durations during their pregnancies. At an average age of 14 months, children underwent a pediatric examination and an evaluation with the Bayley Scales of Infant Development (BSID-II).Duration of in utero exposure to SSRIs was negatively associated with total Apgar scores, specifically the activity subscale. Odds ratios for a low score (<2) on this scale were 3.8 and 6.0 at 1 and 5 min, respectively. Newborns with longer exposure were more often admitted to the Neonatal Intensive Care Unit (p < .03). Mental Development Index scores of the infants were not associated with the length of gestational exposure to SSRIs. A longer duration of exposure increased the risk for lower Psychomotor Developmental Index and Behavioral Rating Scale scores in infancy (p = 0.012 and p = 0.007, respectively) on the BSID-II.The findings provide evidence that the length of prenatal SSRI antidepressant use can affect neonatal adjustment and can have an effect on psychomotor test scores in infancy. Importantly, the children's mental development and motor function by neurological examination were within the normal range. Timing of exposure to SSRIs during susceptible periods of fetal development and variations in the severity of maternal depression may have contributed to the associations.
View details for DOI 10.1007/s00213-011-2270-z
View details for PubMedID 21499702
Movement, imaging and neurobehavioral assessment as predictors of cerebral palsy in preterm infants
JOURNAL OF PERINATOLOGY
2007; 27 (4): 225-229
To study the relative efficacy of three early predictors of cerebral palsy.One Hundred and thirty infants with birth weight <1500 g were recruited. Video recordings of spontaneous general movements were made at 36 and 52 weeks postconceptional age. Magnetic resonance imaging and the neurobehavioral assessment of the preterm infant were done at 36 weeks postconceptional age. Follow-up neurological examination and Bayley assessments were made at 18 months corrected age to make early identification of cerebral palsy.Magnetic resonance imaging gave the best specificity and accuracy of 91 and 84% respectively. General movements at 52 weeks showed an improved specificity and accuracy over performance at 36 weeks postconceptional age. The negative predictive value for all methods tested was between 90 and 97%. Combining the results of magnetic resonance imaging and the neurobehavioral assessment improved the sensitivity of prediction to 80%, suggesting that a holistic approach to early detection of cerebral lesions is preferable to a single test.The majority of infants who appeared to behave within normal limits and exhibit normal brain structure in the newborn period were classified as neurologically intact at follow-up.
View details for DOI 10.1038/sj.jp.7211664
View details for Web of Science ID 000245502400006
View details for PubMedID 17304207
Acute stress disorder among parents of infants in the neonatal intensive care nursery
2006; 47 (3): 206-212
The authors examined the prevalence of acute stress disorder (ASD) in parents of infants hospitalized in the neonatal intensive care unit (NICU). Forty parents were assessed after the birth of their infants. Parents completed self-report measures of ASD, parental stress, family environment, and coping style: 28% of parents developed symptoms of ASD. ASD was associated with female gender, alteration in parental role, family cohesiveness, and emotional restraint. Family environment and parental coping style are significantly associated with the development of trauma symptoms. Results from this study suggest potential interventions to help minimize psychological distress in parents.
View details for Web of Science ID 000237226100003
View details for PubMedID 16684937
Neurobehavioral assessment predicts differential outcome between VLBW and ELBW preterm infants.
Journal of perinatology
2005; 25 (12): 788-793
To evaluate the impact of birth weight on development of very low birth weight (VLBW) infants using the Neurobehavioral Assessment of the Preterm Infant (NAPI) before hospital discharge, and to show the relation to follow-up outcomes at 12, 18 and 30 months of age.In total, 113 preterm infants were assessed with the NAPI at 36 weeks postmenstrual age. Later, neurodevelopment was examined using the Bayley Infant Neurodevelopmental Screener (BINS) at 12 months and the Bayley Scales of Infant Development, at 18 and 30 months. The cohort was divided into two groups, based on birth weight, extremely low birth weight (ELBW) (<1000 g) and VLBW (1000 to 1500 g).ELBW infants showed significantly lower NAPI scores compared with VLBW infants at 36 weeks. The predischarge NAPI scores correlated with the 12, 18 and 30 months scores when the ELBW infants continue to have lower performance than the VLBW infants. In all, 14 infants developed cerebral palsy. These infants had significantly lower NAPI, BINS and Bayley scores compared with all other preterm infants.NAPI before discharge provides clinically meaningful information related to later neurodevelopmental outcome.
View details for PubMedID 16292337
Neonatal brain magnetic resonance imaging before discharge is better than serial cranial ultrasound in predicting cerebral palsy in very low birth weight preterm infants
2004; 114 (4): 992-998
To compare the value of serial cranial ultrasound (US) with a single magnetic resonance imaging (MRI) before discharge in very low birth weight preterm infants to predict cerebral palsy (CP).Infants who weighed <1250 g at birth and were <30 weeks' gestational age underwent conventional brain MRI at near term (36-40 weeks' postmenstrual age) using 1.5 Tesla MRI scanner. Sagittal and axial T1 and T2 fluid attenuated inversion recovery and gradient recalled echo images were obtained. Cranial US was also obtained at least twice during the first 2 weeks of life. MRI and US images were interpreted by 2 independent radiologists, who were masked to clinical outcome, and scored as follows: category 1, no abnormality; category 2, subependymal hemorrhage or mineralization; category 3, moderate to severe ventriculomegaly; category 4, focal parenchymal abnormality with or without ventriculomegaly. For the purpose of this study, 1 and 2 were categorized as "normal," and 3 and 4 were categorized as "abnormal." The infants were assessed at a mean age of 20 and 31 months using the Amiel-Tison standardized neurodevelopmental examination.The sensitivity and specificity of MRI for predicting CP were 71% and 91% at 20 month and 86% and 89% at 31 months, respectively. The sensitivity and specificity of US for predicting CP were 29% and 86% at 20 months and 43% and 82% at 31 months.As a predictor of outcome for CP, MRI at near-term in very low birth weight preterm neonates is superior to US. However, both US and MRI demonstrate high specificity.
View details for DOI 10.1542/peds.2003-0772-L
View details for Web of Science ID 000224242200034
View details for PubMedID 15466096
Neurobehavioral Assessment of the Preterm Infant (NAPI) before discharge may predict neurodevelopmental outcome of VLBW and ELBW infants
INT PEDIATRIC RESEARCH FOUNDATION, INC. 2004: 412A–413A
View details for Web of Science ID 000220591102411
Diffusion tensor brain imaging findings at term-equivalent age may predict neurologic abnormalities in low birth weight preterm infants
AMERICAN JOURNAL OF NEURORADIOLOGY
2003; 24 (8): 1646-1653
Low birth weight preterm infants are at high risk of brain injury, particularly injury to the white matter. Diffusion tensor imaging is thought to be more sensitive than conventional MR imaging for detecting subtle white matter abnormalities. The objective of this study was to examine whether diffusion tensor imaging could detect abnormalities that may be associated with later neurologic abnormalities in infants with otherwise normal or minimally abnormal conventional MR imaging findings.We prospectively studied 137 low birth weight (<1800 g) preterm infants. Neonatal conventional MR imaging and diffusion tensor imaging were performed near term-equivalent age before discharge, and neurologic development of the infants was later followed up at 18 to 24 months of age.Among the preterm infants who were fully studied, 63 underwent normal conventional MR imaging. Three of these infants developed cerebral palsy, and 10 others showed abnormal neurologic outcome. Diffusion tensor imaging results for these infants showed a significant reduction of fractional anisotropy in the posterior limb of the internal capsule in neurologically abnormal infants (including those with cerebral palsy) compared with control preterm infants with normal neurologic outcomes.These results suggest that neonatal diffusion tensor imaging may allow earlier detection of specific anatomic findings of microstructural abnormalities in infants at risk for neurologic abnormalities and disability. The combination of conventional MR imaging and diffusion tensor imaging may increase the predictive value of neonatal MR imaging for later neurologic outcome abnormalities and may become the basis for future interventional clinical studies to improve outcomes.
View details for Web of Science ID 000185400100031
View details for PubMedID 13679287
Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy
1st International Conference on Womens Mental Health
MOSBY-ELSEVIER. 2003: 402–8
To compare the structural growth and developmental outcome of children born to mothers diagnosed with major depressive disorder during pregnancy who were exposed or not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero.Children whose mothers were diagnosed with major depressive disorder in pregnancy and elected not to take medication (n = 13) were compared with children of depressed mothers treated with SSRIs (n = 31) on birth outcomes and postnatal neurodevelopmental functioning between ages 6 and 40 months. Children underwent blinded standardized pediatric and dysmorphology examinations and evaluations of their mental and psychomotor development with the use of the Bayley Scales of Infant Development (BSID II).The Bayley mental developmental indexes were similar in both groups. Children exposed to SSRIs during pregnancy had lower APGAR scores and scored lower on the Bayley psychomotor development indexes and the motor quality factor of the Bayley Behavioral Rating Scale than unexposed children.The findings that SSRIs during fetal development might have subtle effects on motor development and motor control are consistent with the pharmacologic properties of the drugs.
View details for DOI 10.1067/mpd.203.139
View details for Web of Science ID 000182733800011
View details for PubMedID 12712058
The need for long-term audiologic follow-up of neonatal intensive care unit (NICU) graduates
INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY
2003; 67 (4): 353-357
To evaluate the adequacy of newborn hearing screening in the identification of hearing loss in post-neonatal intensive care unit (NICU) infants.Eighty-two post-NICU infants who had initially passed automated auditory brainstem response (AABR) screening were studied prospectively between November 1997 and July 1999. Tympanometry and transient evoked otoacoustic emissions (TEOAE) were used to evaluate middle ear status and screen the hearing of subjects when they were seen routinely in the Mary L. Johnson Infant Development Clinic, where NICU graduates are followed at our institution. TEOAEs were not performed in subjects with abnormal tympanometry, defined as negative pressures greater than 200 daPa or flat tympanograms.Of the 82 subjects, 31 (37%) had abnormal tympanometry in at least one ear, with 24 (29%) exhibiting abnormal values bilaterally. Two subjects were identified with delayed-onset or previously undiagnosed sensorineural hearing loss. One had a history of persistent pulmonary hypertension (PPHN) and extracorporeal membrane oxygenation. The other infant had no risk factors for sensorineural hearing loss.Our data indicate that newborn hearing screening programs may not provide adequate vigilance for NICU graduates. The high incidence of abnormal middle ear status and the identification of delayed-onset hearing loss in an infant without known risk factors highlights the need for close audiologic and speech/language follow-up in the post-NICU population.
View details for DOI 10.1016/S0165-5876(02)00400-7
View details for Web of Science ID 000182263300007
View details for PubMedID 12663106
Diffusion tensor MRI may predict abnormal neurological outcome in preterm infants
INT PEDIATRIC RESEARCH FOUNDATION, INC. 2003: 539A
View details for Web of Science ID 000181897903046
Magnetic resonance imaging (MRI) compared with ultrasound (US) to predict later cerebral palsy in very low birth weight (VLBW) preterm infants
INT PEDIATRIC RESEARCH FOUNDATION, INC. 2003: 543A
View details for Web of Science ID 000181897903071
Quantitative brain magnetic resonance imaging in preterm infants may predict cerebral palsy
INT PEDIATRIC RESEARCH FOUNDATION, INC. 2002: 439A
View details for Web of Science ID 000174714602555
Infant heart transplantation at Stanford: Growth and neurodevelopmental outcome
2002; 109 (1): 1-7
To evaluate the growth and neurodevelopmental outcome of 18 surviving Stanford patients who received heart transplantations before their second birthday.We compared the growth and neurodevelopmental outcome of these 18 patients with a second group of age-matched comparison patients who underwent other heart surgery requiring cardiopulmonary bypass.Difficulties with growth and development were more common in the transplant group as were neurologic abnormalities. Speech and language delays as well as hearing problems were also more common in the transplant group.Multicenter prospective longitudinal neurodevelopmental outcome studies of infant heart transplant patients should be conducted to provide a more efficient basis for evaluating management protocols and assessment of long-term outcomes and of the need for early intervention services.
View details for Web of Science ID 000173006600019
View details for PubMedID 11773534
Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993-1994
Annual Meeting of the Society-for-Pediatric-Research
AMER ACAD PEDIATRICS. 2000: 1216–26
The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401-1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes.A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months' corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome.Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 +/- 135 g, mean gestation (best obstetric dates) 26 +/- 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index <70, 29% had a Psychomotor Developmental Index <70, 9% had vision impairment, and 11% had hearing impairment. Neurologic, developmental, neurosensory, and functional morbidities increased with decreasing birth weight. Factors significantly associated with increased neurodevelopmental morbidity included chronic lung disease, grades 3 to 4 intraventricular hemorrhage/periventricular leukomalacia, steroids for chronic lung disease, necrotizing enterocolitis, and male gender. Factors significantly associated with decreased morbidity included increased birth weight, female gender, higher maternal education, and white race.ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months' corrected age.
View details for Web of Science ID 000087441400021
View details for PubMedID 10835060
Inhaled nitric oxide in term and near-term infants: Neurodevelopmental follow-up of The Neonatal Inhaled Nitric Oxide Study Group (NINOS)
JOURNAL OF PEDIATRICS
2000; 136 (5): 611-617
Inhaled nitric oxide (INO) improved oxygenation and reduced the occurrence of death or extracorporeal membrane oxygenation in term and near-term hypoxic neonates. We report the results of neurodevelopmental follow-up of infants enrolled in the NINOS trial.Hypoxic infants >/=34 weeks' gestation and <14 days of age were randomized to 20 ppm INO or 100% oxygen as control. Comprehensive neurodevelopmental assessment of survivors occurred at 18 to 24 months of age.A total of 235 infants were enrolled in the original trial. There were 36 deaths, 20 of 121 infants in the control group and 16 of 114 infants in the INO-treated group. Of the 199 surviving infants, 173 (86.9%) were seen for follow-up (88 members of the control group and 85 members of the INO-treated group), and 135 infants were normal (69 [79.3%] members of the control group and 66 [77.6%] members of the INO-treated group). Twenty-two infants had sensorineural hearing loss (12 members of the control group and 10 members of the INO-treated group). Moderate to severe cerebral palsy occurred in 13 infants (7 infants in the control group and 6 infants in the INO-treated group). Mental developmental index scores (87 +/- 18.7 in the control group vs 85 +/- 21.7 in the INO-treated group) and psychomotor developmental index scores (93.6 +/- 17.5 in the control group vs 85.7 +/- 21.2 in the INO-treated group) were not different. A total of 29.6% of the control group compared with 34.5% of the INO-treated group had at least one disability. Infants with congenital diaphragmatic hernia, enrolled in a separate but parallel trial, had similar outcomes with a higher incidence of sensorineural hearing loss.Inhaled nitric oxide is not associated with an increase in neurodevelopmental, behavioral, or medical abnormalities at 2 years of age.
View details for Web of Science ID 000086985900011
View details for PubMedID 10802492
Effects of skin-to-skin holding on general movements of preterm infants
1999; 38 (8): 467-471
The study objective was to test the hypothesis that the effect of skin-to-skin (STS) holding increases the ratio of rest to activity in low birth weight preterm infants. Ten infants with birthweight < 2,000 grams were videotaped before and after STS holding. Video recordings were analyzed to determine the number of general movements. We found no statistically significant difference between the percentage of general movements over the two periods. We conclude that the ratio of rest-activity before and after STS holding does not change as measured by occurrence of general movements.
View details for Web of Science ID 000081864400005
View details for PubMedID 10456242
Supplemental oxygen may decrease progression of prethreshold disease to threshold retinopathy of prematurity.
Journal of perinatology
1997; 17 (6): 434-438
The optimum level of oxygen saturation for infants with prethreshold retinopathy of prematurity (ROP) is unknown. We reviewed our conversion rate from prethreshold to threshold ROP between 1985 and 1993 during which time target levels of oxygen saturation rose in a stepwise fashion. A retrospective study of 153 infants with prethreshold ROP was performed at Stanford University between 1985 and 1993 that showed that target minimum oxygen saturation rose from 92% (1985-1987) to 95% (1988) to 96% (1989) to 99% (1990-1993). In addition, we looked at 26 infants between 1994 and 1996 who were excluded from the STOP-ROP study and who were not receiving supplemental oxygen in an effort to maintain equipoise for that study. Infant characteristics were tabulated, and rates of progression from prethreshold to threshold ROP were calculated. Rates of progression to threshold varied little between 1985 and 1989 (average 37%), but dropped to 7% for the period between 1990 and 1993. From 1994 through 1996 the rate of progression to threshold disease rose again, to 38%. Moderate supplemental oxygen (target saturation 99% with PO2 no higher than 100 mm Hg) was associated with regression of prethreshold ROP, without appearing to arrest retinal vascular maturation.
View details for PubMedID 9447528
Neonatal severity of illness scoring systems: A comparison
1997; 36 (4): 223-227
Several different scoring systems have been developed to predict neonatal morbidity and mortality. In this investigation we compared the utility of four severity of illness scoring systems (SISS) as predictors of days on ventilatory (DOV), length of hospital stay (LOS), and mortality in very-low-birth weight (VLBW) premature infants who required mechanical ventilation. The SISS assessed were the Score for Neonatal Acute Physiology (SNAP); the Score for Neonatal Acute Physiology-Perinatal Extension (SNAP + PE); Clinical Risk Index for Babies (CRIB), and the Sinkin Score at 12 hours (SS12). Results revealed significant correlations among the SS12, SNAP, SNAP + PE, CRIB, birth weight (BW), DOV, and LOS. However, none of the systems we assessed offered striking advantage over BW in a VLBW ventilated group.
View details for PubMedID 9114994
Sedation administered to very low birth weight premature infants.
Journal of perinatology
1997; 17 (2): 107-112
The aim of this study was to evaluate the impact of individualized developmental care for very low birth weight infants on the amount of sedation used in their treatment.A randomized control trial was conducted. Each infant in the experimental group underwent evaluation weekly, and individualized behaviorally oriented care plans, aimed at reducing stress and promoting self-regulatory behaviors, were prepared and implemented. Control infants received the usual standard of nursery care. Total doses of opioids and chloral hydrate were calculated. Severity of illness during the initial hospital stay was stratified with use of the Neonatal Medical Index.Severely ill infants in the treatment group required less chloral hydrate than those in the control group. Infants who were not severely ill received little or no sedation, and among this subgroup treatment and control infants did not differ.We speculate that developmentally based care reduces stress levels in severely ill very low birth weight infants and thus decreases sedation requirements.
View details for PubMedID 9134507
INDIVIDUALIZED DEVELOPMENTAL CARE FOR VERY-LOW-BIRTH-WEIGHT PREMATURE-INFANTS
1995; 34 (10): 523-529
Forty very-low-birth-weight neonatal intensive care unit (NICU) infants with birth weights < or = 1,250 g were randomly assigned to treatment or control groups. Behavior of the treatment infants was systematically evaluated, and individualized developmentally oriented care plans were implemented to enhance stability. Treatment babies required fewer days of intermittent mandatory ventilation and continuous positive airway pressure and achieved full enteral feedings sooner. Length of hospital stay and hospital charges were less for treatment than control infants. There were favorable effects on treatment infants' behavioral performance at 42 weeks' postconceptional age. These results support the hypothesis that behaviorally sensitive, developmentally oriented care improves medical and neurodevelopmental outcome in the NICU.
View details for Web of Science ID A1995RZ28800003
View details for PubMedID 8591679
INTRACRANIAL ABNORMALITIES AND NEURODEVELOPMENTAL STATUS AFTER VENOVENOUS EXTRACORPOREAL MEMBRANE-OXYGENATION
JOURNAL OF PEDIATRICS
1994; 125 (2): 304-307
Computed tomography scans of the head and early neurodevelopmental assessment (Bayley Scales of Infant development) were recorded for 24 surviving infants who received venovenous extracorporeal membrane oxygenation and were compared with those of infants treated with venoarterial bypass matched by diagnosis and oxygenation index before extracorporeal membrane oxygenation. A comparable neuroradiographic and early neurodevelopmental outcome was documented for survivors of venoarterial and venovenous extracorporeal membrane oxygenation.
View details for Web of Science ID A1994PA95200025
View details for PubMedID 8040782
- INGESTION OF A LARYNGOSCOPE LIGHT-BULB DURING DELIVERY ROOM RESUSCITATION PEDIATRICS 1991; 87 (4): 581-582
LUNG PROFILE - SEX-DIFFERENCES IN NORMAL-PREGNANCY
OBSTETRICS AND GYNECOLOGY
1985; 66 (3): 327-330
The incidence of respiratory distress syndrome (RDS) is higher in male than in female infants. The lung profiles--lecithin/sphingomyelin (L/S) ratios, percent disaturated (acetone precipitated) lecithin, phosphatidylglycerol, and phosphatidylinositol--were obtained in amniotic fluid during 164 normal pregnancies of 30 or more weeks' gestation. The profiles were evaluated to determine any sex differences in fetal development of the surfactant components. According to regression analysis the L/S ratios for females reached 2:1 at 33.7 weeks, which is 1.4 weeks earlier than males. A similar trend was evident for disaturated lecithin. Phosphatidylglycerol first appeared at 34 weeks' gestation for females and 35 weeks for males. The rate of the increase in phosphatidylglycerol was higher in females than in males. Phosphatidylinositol began to decrease after 36 weeks for females and fell to levels below that of males after 37 weeks' gestation. All four indexes of the lung profile revealed a higher degree of lung maturity in female than in male fetuses during the last two months of normal pregnancy. This explains a higher incidence of RDS in male than in female infants.
View details for Web of Science ID A1985APU2500006
View details for PubMedID 4022494